DNA glycosylases: in DNA repair and beyond

The base excision repair machinery protects DNA in cells from the damaging effects of oxidation, alkylation, and deamination; it is specialized to fix single-base damage in the form of small chemical modifications. Base modifications can be mutagenic and/or cytotoxic, depending on how they interfere with the template function of the DNA during replication and transcription. DNA glycosylases play a key role in the elimination of such DNA lesions; they recognize and excise damaged bases, thereby initiating a repair process that restores the regular DNA structure with high accuracy. All glycosylases share a common mode of action for damage recognition; they flip bases out of the DNA helix into a selective active site pocket, the architecture of which permits a sensitive detection of even minor base irregularities. Within the past few years, it has become clear that nature has exploited this ability to read the chemical structure of DNA bases for purposes other than canonical DNA repair. DNA glycosylases have been brought into context with molecular processes relating to innate and adaptive immunity as well as to the control of DNA methylation and epigenetic stability. Here, we summarize the key structural and mechanistic features of DNA glycosylases with a special focus on the mammalian enzymes, and then review the evidence for the newly emerging biological functions beyond the protection of genome integrity

Physiological analysis of mutants indicates involvement of the Saccharomyces cerevisiae GPI-anchored protein gp115 in morphogenesis and cell separation.

This paper reports a phenotypic characterization of ggp1 mutants. The cloned GGP1 (GAS1) gene, which encodes a major GPI-anchored glycoprotein (gp115) of Saccharomyces cerevisiae of unknown function, was used to direct the inactivation of the chromosomal gene in haploid and diploid strains by gene replacement. The analysis of the null mutants reveals a reduction in the growth rate of 15 to 40%. Cells are round, with more than one bud, and extensively vacuolized. In the stationary phase, mutant cells are very large, arrest with a high percentage of budded cells (about 54 and 70% for haploid and diploid null mutants, respectively, in comparison with about 10 to 13% for control cells), and have reduced viability. The observed phenotype suggests defects in cell separation. Flow cytometric analysis of DNA reveals an increase in the fraction of cells in the G2+M+G1* compartment during exponential growth. Conjugation and sporulation are not affected. The exocellular location of gp115 led us to examine cell wall properties. Cell wall and septum ultrastructure of abnormally budded cells was analyzed by electron microscopy analysis, and no appreciable differences from wild-type cells were found. Microscopic analysis revealed an increase in chitin content and delocalization. In comparison with control cells, ggp1 null mutants are shown to be resistant to Zymolyase during the exponential growth phase. A fivefold overexpression of gp115 does not bring about any effects on cell growth parameters and cell wall properties

DOLCE: A descriptive ontology for linguistic and cognitive engineering

DOLCE, the first top-level (foundational) ontology to be axiomatized, has remained stable for twenty years and today is broadly used in a variety of domains. DOLCE is inspired by cognitive and linguistic considerations and aims to model a commonsense view of reality, like the one human beings exploit in everyday life in areas as diverse as socio-technical systems, manufacturing, financial transactions and cultural heritage. DOLCE clearly lists the ontological choices it is based upon, relies on philosophical principles, is richly formalized, and is built according to well-established ontological methodologies, e.g. OntoClean. Because of these features, it has inspired most of the existing top-level ontologies and has been used to develop or improve standards and public domain resources (e.g. CIDOC CRM, DBpedia and WordNet). Being a foundational ontology, DOLCE is not directly concerned with domain knowledge. Its purpose is to provide the general categories and relations needed to give a coherent view of reality, to integrate domain knowledge, and to mediate across domains. In these 20 years DOLCE has shown that applied ontologies can be stable and that interoperability across reference and domain ontologies is a reality. This paper briefly introduces the ontology and shows how to use it on a few modeling cases

A Methodology to Validate Interactive Storytelling Scenarios in Linear Logic

Abstract. Debugging is one of the main requirements for Interactive Storytelling (IS) authoring tools. During the authoring phase, authors have to specify large numbers of rules and actions as well as consider many possible paths. As a consequence, flaws may happen and finding them “by hand ” is complex. Therefore the validation of an IS becomes a crucial issue and automatic assistance in this process is needful. Originated from those requirements, we propose, within the framework of this paper, a methodology using Linear Logic, based on analyzing automatically the resource allocation mechanisms, that helps authors derive a valid scenario of an IS. To do this, we model a scenario by a Linear Logic sequent, then prove the received sequent, which allows building and examining automatically all the possible branches in the scenario, thereby authors may guarantee that all the decisions (that may be made while unfolding the IS) lead to satisfactory endings of their goals. The paper ends with an example on an extract of an educational game to illustrate the methodology